Hye Duck Yeom , Jihwon Yun , Chaewon Seo , Mee-Hyun Lee , Gihyun Lee , Junho H Lee
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引用次数: 0
Abstract
This study examines the effects of three Tripterygium wilfordii compounds—celastrol, triptolide, and triptonide—on 5-HT3A receptors. Using two-electrode voltage-clamp recordings, we found all three compounds reversibly and concentration-dependently inhibited 5-HT-induced inward currents (I5-HT), with celastrol showing the strongest inhibition (∼83 % at 100 µM) compared to triptolide (∼40 %) and triptonide (∼30 %) at 300 µM. Their voltage- and use-independent inhibition suggests they are not open-channel blockers. Further molecular docking and mutational analysis revealed celastrol binds to K127 and Y114, with mutations at these sites significantly reducing its inhibitory effect. Overall, celastrol, triptolide, and triptonide may suppress hyperactive gut signaling via 5-HT3A inhibition, with celastrol emerging as a promising therapeutic candidate.
期刊介绍:
Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.